Typical devices for measuring the ionic content of solutions include a reference electrode and a separate potentiometric or "working" electrode. When these are immersed in a volume of solution to be analyzed, the reference and working electrodes together constitute an electrochemical cell. The reference electrode provides a constant potential with respect to which is measured the potential developed by the working electrode from the solution. The potential difference across the cell is proportional to the logarithm of the activity of the ion. This in turn is related to the concentration of the ion in the solution, such that the concentration can be directly determined as a function of the voltage measured across the reference and working electrodes.
Many documents discuss designs for and methods for fabrication of ion-sensitive devices for measuring the ionic content of solutions. For example, U.S. Pat. No. 4,613,442 issued to the present inventor shows an "Ambient Sensing Device" suitable for use at high temperatures. Other documents include European Patent Application 129,233 to Salman et al.; "A Batch-Processed Reference Micro Electrode Integrated on a Silicon Substrate", Sinsabaugh et al., in Electrochemical Sensors for Biomedical Applications, pp. 66-73 (1986); "Characteristics of Reference Electrodes Using a Polymer Gate ISFET", Matsuo et al., in Sensors and Actuators, 5 (1984), pp. 293-305; "An Integrated Sensor for Electrochemical Measurements", Smith et al., in IEEE Transactions on Biomedical Engineering, Vol. BME-33, No. 2, (1986) pp. 83-90; U.S. Pat. No. 4,592,824 to Smith et al., the disclosure of which appears to be comparable to that of the Smith et al. paper; ".sctn.3.7. Reference ISFET," in "Chemically Sensitive Field Effect Transistors"; Janata et al., in Ion-Selective Electrodes in Analytical Chemistry, vol. 2, (1980), pp. 161-167; Ion-Selective Electrode Methodology, vol. 1, (Covington ed.), pp. 58-62 (1979); Ion-Selective Electrodes in Analytical Chemistry, vol. 1, (Freiser ed.), especially chapter 3.3, "Reference Electrodes", pp. 323-331 (1978); and U.S. Pat. Nos. 4,437,969 to Covington et al. and 4,214,968 to Battaglia et al. See also "Chemically Sensitive Potentiometric Microsensors", by the present inventor, Stanford Research Institute (1983), pp. 192-241.
Typical reference electrodes comprise a layer of a material reversible to an ion X, that is, a material which is capable of undergoing a reversible change in oxidation state in response to the relative presence or absence of the ion X. Such materials include metal-halide salts, alloys or compounds. Conveniently this material is formed on the surface of an underlying metallic member. This reference electrode is then overlaid by an electrolyte. The electrolyte illustratively contains a quantity of the ion X dispersed into an aqueous medium, or into a polymeric material. For example, the electrolyte may comprise a gel containing a compound including the ion X. The gel is essentially impervious to mixing with the solution to be analyzed while permitting ion transport therethrough by diffusion. Alternatively the electrolyte may be confined behind a membrane, e.g. cellulose acetate or a porous glass or ceramic or the like, which permits ion transport while restraining flow of the solution and the electrolyte itself. A "liquid junction" is thus formed between the electrolyte and the test solution, which allows flow of ions by diffusion but not by convection.
When the composition of the electrolyte phase is suitably adjusted so that it contains ions at relatively high concentrations of closely similar mobilities, these ions traverse the liquid junction boundary in such a way as to provide electrical continuity between the electrode and the test solution (as required to perform the potentiometric measurement) and maintain a constant (and small) potential difference across the liquid junction boundary, regardless of the composition of the test solution. The potential difference between the electrode reversible to an ion X and its contacting electrolyte depends on the concentration of ion X in this electrolyte. Therefore, when ion X is at a constant concentration, the electrode potential of this electrode is independent of the composition of the solution contacting the liquid junction, which is the requirement for it to be a properly functioning reference electrode. Since ions must freely transport across the liquid junction boundary, constancy of ion X concentration can only be maintained if the electrolyte is a relatively large reservoir for ion X so that ion concentration in the electrolyte remains substantially constant over the time the reference electrode is in use.
Prior art macro-reference electrodes typically consist of a silver chloride coated silver wire dipped into a concentrated potassium chloride solution (or some equivalent formulation) contained in a tubular sleeve typically one-half inch in diameter by a few inches long. The volume of the electrolyte reservoir is several cm.sup.3.
In a typical operational arrangement, the working and reference electrodes are sequentially exposed to, for example, a blood sample and a reagent containing a known concentration of the ions to be measured. By comparison of the potential difference between the reference and working electrodes responsive to the sample and the reagent, an accurately calibrated value can be determined for the concentration of the ion in the blood.
In order to provide a reference electrode which is useful in numerous processes, e.g. for blood analysis operations in hospitals, blood chemistry labs and the like, it is desirable to provide an electrode which is inexpensive, so as to be economically disposable, which is small, to allow use with small samples, and which has a long shelf life. The fact that most prior electrodes have employed hydrophilic or aqueous reference electrolytes make the long shelf life goal particularly difficult to achieve. Typically hydrophilic electrolytes have been hydrated gels or the like to allow ion transport. To ship and store such "wet" electrolytes involves a relatively complex packaging and storage problem. Alternatively the gels can be shipped dry and be hydrated prior to use, but this can cause further operational problems to arise, in particular, because of the size of such dry electrodes, the time it takes to properly hydrate them for use would significantly detract from their usability. A further difficulty is the physical size of prior art reference electrodes.